One year comparative trial of metformin and glipizide in type 2 diabetes mellitus.

Forty-eight diabetic subjects with diet-failed Type 2 mellitus, aged 40-69 years, were randomised to metformin (24 patients) or glipizide (24 patients) therapy, and followed prospectively for 12 months. Most subjects were obese. Metformin gave better fasting plasma glucose control compared to glipizide at 24 (p < 0.01), 36 (p < 0.05) and 52 weeks (p < 0.05) with a lower HbA1 concentration at 52 weeks (p < 0.05). Metformin treated patients lost weight whereas glipizide treated subjects gained weight. The weight change between the treatment groups reached significance at 4 weeks (p < 0.05) and was highly significant (p < 0.001) at 8, 12, 24, 36 and 52 weeks. There were no significant changes in either fasting plasma lipid or blood lactate levels in either the metformin or glipizide treated groups. Both drugs caused a similar reduction in albumin excretion rates. In conclusion, metformin gave better glycaemic control than glipizide, with weight loss rather than weight gain in obese Type 2 patients.

The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

1. Renal function was assessed in 10 healthy female volunteers during administration of placebo, paracetamol (acetaminophen) (4.0 g daily) and indomethacin (150 mg daily) for 3 days under conditions of controlled sodium and fluid intake. 2. Paracetamol and indomethacin had no significant effect on the glomerular filtration rate and effective renal plasma flow as measured by the renal clearances of inulin, creatinine and p-aminohippurate (PAH). 3. Compared with placebo, paracetamol reduced the mean urinary excretion of prostaglandin E2 by 43% on the second day and 58% on the third treatment day (P less than 0.01). With indomethacin the corresponding reductions were 73 and 80%. Paracetamol and indomethacin had much less effect on the excretion of prostaglandin 6-keto F1 alpha, and a significant decrease was observed only on the third day. 4. The decreased urinary excretion of prostaglandin E2, produced by paracetamol was associated with a reduction in sodium excretion of more than 50% (P less than 0.01) and delay in the onset of diuresis following an acute water load. 5. The renal effects of paracetamol and indomethacin appear to differ. Although indomethacin reduced prostaglandin excretion more than paracetamol it had a similar effect on sodium excretion and less initial antidiuretic action. Unlike paracetamol, indomethacin also reduced basal plasma renin activity. 6. Paracetamol reduced the total body clearance of PAH and increased its plasma half-life. This effect could be attributed to inhibition of the acetylation of PAH by paracetamol. 7. In normal use paracetamol does not appear to have the adverse renal effects associated with the non-steroidal anti-inflammatory analgesics and further studies are required to establish the clinical significance of these findings.

Fulminant hyperkalaemia and multiple complications following ibuprofen overdose.

A previously healthy 17-year-old man was admitted in coma following major overdosage with ibuprofen and minor overdosage of doxepin (plasma concentrations 809 and 0.49 mg/L, respectively). Initially, potassium chloride (20 mmol 3-hourly) was infused because of mild hypokalaemia (K+ 2.8 mmol/L). 14 hours after admission the patient developed a hypermetabolic state with pyrexia, metabolic acidosis and progressive respiratory failure despite ventilation at 16 L/min, and a malignant broad complex tachycardia was associated with acute hyperkalaemia (K+ 8.3 mmol/L). The arrhythmia resolved with correction of the hyperkalaemia. Chest x-rays showed diffuse opacification throughout both lung fields and subsequently there was transient impairment of renal function, with evidence of mild rhabdomyolysis. Ventilatory support was required for 60 hours and a chest x-ray at 6 days showed extensive bilateral nodular shadowing, which was still present at follow-up 4 weeks later.

Leptospira icterohaemorrhagiae infection presenting as acute renal failure.

The features of leptospiral infection should be sought in all cases of acute renal failure since management depends on the recognition of the clinical syndrome and serological confirmation is usually delayed. Hepatic and renal involvement is usual but renal failure without significant derangement of liver function is described.

Metformin efficacy and tolerance in obese non-insulin dependent diabetics: a comparison of two dosage schedules.

A comparative open study of metformin unit doses of 500 mg and 850 mg was carried out in 64 obese, non-insulin dependent diabetics on 1.5 to 3 g metformin daily. Glycaemic response, blood lactate, plasma metformin concentrations and tolerance for metformin were assessed. On changing from a 500 mg unit dose to an equivalent total dose of metformin using the 850 mg preparation, there were no significant changes in the random blood glucose, glycated haemoglobin, or blood lactate concentrations. Metformin plasma concentrations remained unchanged except for patients transferred from 1.5 to 2.0 g daily to 850 mg twice daily; in these patients plasma concentrations increased from 1.83 +/- 0.87 to 2.50 +/- 0.89 micrograms/l (p less than 0.01). Seven patients (3 asymptomatic and 4 with background symptoms) became intolerant of the 850 mg regimen and required to return to the 500 mg dose regimen. After exclusion of patients intolerant of the 850 mg dose regimen (11%), the remaining patients noted no significant change in symptoms and 28% of all patients transferred to the 850 mg dose unit indicated an overall preference for this regimen.

Effects of improved glycaemic control on calcium and magnesium homeostasis in type II diabetes.

Poorly controlled type II diabetic patients with hypomagnesaemia, hypermagnesuria, and hypercalciuria were allocated to treatment with either metformin or glipizide, to determine the effects on some indices of mineral metabolism. Despite comparable improvement in glycaemic control, assessed by glucose and haemoglobin A1, there were significant differences between the two groups in the handling of magnesium. Patients receiving metformin showed a reduction in magnesium excretion but remained hypomagnesaemic and hypercalciuric. In contrast, patients receiving glipizide exhibited little change in either magnesium or calcium excretion but showed a significant rise in serum magnesium.

Cranial diabetes insipidus secondary to arrested hydrocephalus.

An unusual case is described linking cranial diabetes insipidus with longstanding arrested hydrocephalus. The latter was demonstrated by computed tomographic (CT) and nuclear magnetic resonance (NMR) scans and cerebrospinal fluid pressure measurements. The increasing use of CT and NMR scans may result in this association of cranial diabetes and hydrocephalus being better defined.